Symposien Freitag

Progression of age-related macular degeneration (AMD) includes hallmarks of retinal pigment epithelium and photoreceptor loss accompanied by unchecked immune response and degeneration or pathological angiogenesis. While the current paradigm converges to associate complement dysregulation and inflammasome activation as major components of immune responses, we interrogate the specific mechanisms of action of macrophage and myeloid cells within the retina. To that end we have shown how macrophages are early infiltrating cells that engulf dying RPE and drive angiogenesis and that this response may be subverted through cytokine modulation ((L-4, IL-33) of macrophage function or through activation of inhibitory receptors (CD200R). Furthermore our investigations have shown that it is the nature of RPE degeneration (oxidative stress, bio-energetic switching or impaired autophagy) that differentially regulate macrophage phenotype and function and drive angiogenesis.

The definition of retinal microglia (MG) has so far been hampered by the lack of genetic in vivo approaches that enables to discriminate MG from closely related peripheral macrophages. Here we introduce a novel experimental mouse model that specifically targets MG and allows to examine the origin and turnover of MG in the steady state as well as to study the function of the transforming-growth-factor-b-activated kinase 1 (TAK1) in MG during laser induced CNV development.

IFN beta therapy is an accepted treatment for multiple sclerosis. Using the mouse model of laser-induced retinal damage and choroidal neovascularization we provide evidence that IFN beta also potently modulates retinal inflammation. Laser damage was significantly augmented in INFNAR knock out mice whereas treatment of wild type mice with IFN beta reduced microglial reactivity and CNV leakage. We hypothesize that the well known principle of IFN beta therapy could be potentially applied to conditions of retinal inflammation and neovascularization.

The causes for glaucoma are not understood yet. In an autoimmune glaucoma model RGC loss and axon degeneration can be induced by immunizing with ocular antigens. Microglia are involved in the initial stages of cell decline, which could hint at a destructive impact of retinal microglia. At this Point in time the complement system is also activated.It appears that astrocytes are involved in cell loss processes, in later stages.

Juvenile idiopathic arthritis associated uveitis (JIAU) is the most common uveitis entity in childhood. Little is known about the pathogenesis of disease. S100A8/A9 and -A12 proteins are secreted by phagocytes, and are valuable biomarkers in childhood arthritis. In JIAU, active disease is associated with increased serum S100A8/A9 and -A12 levels. Peripheral blood monocyte subtypes are also up-regulated. Monocytes and S100 proteins may have pro-inflammatory and immunoregulatory functions in JIAU.